Kidney cancer with thyroid metastasis combined with thyroid carcinoma, a case report.

BACKGROUND: Thyroid cancer is the most common malignant tumor of the endocrine system. There have been some reports on kidney cancer with thyroid metastasis. However, kidney cancer has rarely been detected during thyroid cancer surgery. CASE PRESENTATION: We present a rare case of kidney cancer with thyroid metastasis, combined with thyroid carcinoma. A 66-year-old woman was admitted to our hospital in September 2021 due to enlarged left thyroid nodules for two years. The patient was diagnosed with a left thyroid nodule on physical examination in 2012. Extended radical resection of the thyroid cancer was performed. Intraoperatively, two thyroid lesions were identified. Thus, the patient was definitively diagnosed with kidney cancer with thyroid metastasis and papillary thyroid carcinoma. Furthermore, two metastatic nodules due to kidney cancer and one metastatic lymph node lesion due to thyroid cancer were found in the loose connective tissue adjacent to the thyroid. CONCLUSIONS: Kidney cancer with thyroid metastasis and thyroid carcinoma rarely co-occur, and it is difficult to identify the primary tumor. Although clinical examination methods are increasingly updated, the past medical history and physical examination are still very important.

Outcomes of ureteroscopy and internal ureteral stent for pregnancy with urolithiasis: a systematic review and meta-analysis.

OBJECTIVES: To investigate the outcomes of internal ureteral stents in comparison with ureteroscopy (URS) for pregnant women with urolithiasis. DATA SOURCES: Relevant studies published from January 1980 to June 2022 were identified through systematic literature searches of MEDLINE, EMBASE, Web of Science and the Cochrane Library. METHODS OF STUDY SELECTION: A total of 499 studies were initially identified. We included pregnant women in any stages of gestation who underwent double-J (D-J) stent insertion only or ureteroscopy for the treatment of urolithiasis; for a study to be included, the number of participants needed to exceed 10. This systematic review was registered on the PROSPERO website (Reference: CRD42020195607). RESULTS: A total of 25 studies were identified with 131 cases undergoing serial stenting and 789 cases undergoing URS. The pooled operative success rate was 97% for D-J stent insertion and 99% for URS. Only a few patients passed stones spontaneously after serial D-J stenting. The pooled stone free rate (SFR) in URS operations was about 91%. For internal ureteral stent therapy, the rate of normal fertility outcomes was 99%, although the pooled incidence of complications was approximately 45%. For group receiving URS treatment, the rate of normal fertility outcome was 99% and the pooled incidence of complications was approximately 1%. However, the pooled rate of premature birth and abortion were the similar between the two groups (< 1%); the rate of serious complications was also similar between the two groups. CONCLUSIONS: Although internal ureteral stents may cause more minor complications, both ureteroscopy and internal ureteral stents showed had low rates of adverse effects on fertility outcomes when used to treat pregnant women with symptomatic urolithiasis. Evidence suggests that URS may have a greater advantage for pregnant patients with urinary stones when conditions permit. Since, it has been proven to be safe and effective, internal ureteral stents could be considered in emergency or other special situations.

An experimental model of the epithelial to mesenchymal transition and pro-fibrogenesis in urothelial cells related to bladder pain syndrome/interstitial cystitis.

BACKGROUND: Suitable in vitro models are needed to investigate urothelial epithelial to mesenchymal transition (EMT) and pro-fibrogenesis phenotype in bladder pain syndrome/interstitial cystitis (BPS/IC). This study is to establish a novel experimental BPS/IC cell model and explore how different concentrations of tumor necrosis factor (TNF)-α influence the EMT and pro-fibrogenesis phenotype of urothelial cells. METHODS: SV-HUC-1 urothelial cells were cultured with 2, 10, or 50 ng/mL TNF-α to mimic chronic inflammatory stimulation. The EMT and pro-fibrogenesis phenotype, including production of collagen I and pro-fibrosis cytokines, were estimated after 72 h of culture. RESULTS: The bladder urothelial cells of BPS/IC exhibited upregulated vimentin, TNF-α and TNF receptor, downregulated E-cadherin, and increased collagen I. Higher concentrations of TNF-α (10 and 50 ng/mL) produced an obvious mesenchymal morphology, enhanced invasion and migratory capacity, increased expression of vimentin, and decreased expression of E-cadherin. Collagen I was increased in cells treated with 2 and 10 ng/mL TNF-α after 72 h. Secretion of interleukin (IL)-6 and IL-8 was promoted with 10 and 50 ng/mL TNF-α, while that of IL-1ß or transforming growth factor-ß was unaffected. Slug and Smad2 were upregulated by TNF-α after 72 h. The Smad pathway was activated most strongly with 10 ng/mL TNF-α and Slug pathway activation was positively correlated with the concentration of TNF-α. CONCLUSIONS: Sustained 10 ng/mL TNF-α stimulation induced the EMT and pro-fibrogenesis phenotype resembling BPS/IC in SV-HUC-1 cells. Minor inflammatory stimulation induced the pro-fibrogenesis phenotype while severe inflammatory stimulation was more likely to produce significant EMT changes. Different degrees of activation of the Slug and Smad pathways may underlie this phenomenon.

IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way.

BACKGROUND: Insulin-like growth factor 2 (IGF2) messenger RNA binding protein 3 (IMP3) has been testified to be overexpressed in prostate cancer and strongly related to patients' poor prognosis. However, the functions of IMP3 and the underlying mechanisms in prostate cancer still remain unknown. Therefore, the current study was carried out to reveal the role and molecular mechanism of IMP3 in prostate cancer progression. METHODS: The expression levels of IMP3 in prostate cancer tissues and cells were detected by immunohistochemistry (IHC), western blotting and RT-PCR. CCK-8, clone formation, flow cytometry and in vivo tumor formation assays were used to determine cell growth, clone formation apoptosis and tumorigenesis, respectively. The effect of IMP3 on the expression levels of the key proteins in PI3K/AKT/mTOR signaling pathway, including PIP2, PIP3, p-AKT, AKT, p-mTOR, mTOR, PTEN and BAD activation of was determined by western blotting. IP (Immunoprecipitation) assay was used to evaluate the effects of IMP3 and SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) on the ubiquitination of PTEN protein. RESULTS: IMP3 expression level was significantly increased in prostate cancer tissues and cell lines (LNCap, PC3 and DU145) as compared with the paracancerous normal tissues and cells (RWPE-1), respectively. High expression of IMP3 apparently promoted cell viability, tumorigenesis and inhibited cell apoptosis in prostate cancer LNCap, DU145 and PC3 cell lines. In mechanism, IMP3 upregulation significantly increased the phosphorylation levels of AKT and mTOR, and elevated PIP3 expression level, while induced significant reductions in the expression levels of BAD, PTEN and PIP2. And, IMP3 overexpression increased SMURF1 expression, which facilitated PTEN ubiquitination. In addition, SMURF1 overexpression enhanced prostate cancer cell viability and inhibited cell apoptosis. Silence of SMURF1 rescued the enhancements in cell proliferation and tumorigenesis and the inhibition in cell apoptosis rates induced by IMP3 in prostate cancer DU145 and LNCap cells. CONCLUSION: This study reveals that IMP3 is overdressed in prostate cancer, which accelerates the progression of prostate cancer through activating PI3K/AKT/mTOR signaling pathway via increasing SMURF1-mediated PTEN ubiquitination.

IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model.

BACKGROUND: Prostate cancer is one of the most common adult malignancies in men, and nearly all patients with metastatic prostate cancer can develop and receive resistance to primary androgen deprivation therapy (ADT), a state known as metastatic castration-resistant prostate cancer (mCRPC). Recent reports demonstrated the great breakthroughs made by the chimeric antigen receptor T (CAR-T) cell therapy, which is significantly different from traditional T cells therapies. In spite of the progress of CAR-T technology in the treatment of lymphoma, leukemia, and other blood system tumor, there are still many difficulties in the treatment of solid tumors by CAR-T technology. METHODS: In this report, we designed a panel of IL23mAb-PSMA-CARs, including PSMA-CAR, IL23mAb-T2A-PSMA-CAR, IL23mAb-PSMA-CAR, and PSMA-CAR (soluble IL23mAb). And we studied the function of these CARs in mice model. RESULTS: Co-culture experiments with different CAR T cells have normal lysis function in vitro. The duo-CAR T cells co-expressing the IL-23mAb and PSMA-mAb had a significant higher population than the rest three different CAR T cells in co-culturing experiments at day 28, 35 and 42. A panel of cytokines were differentially secreted at higher amounts in IL23mAb-T2A-PSMA-CAR T cells than CAR T cells in other groups. In NOD/SCID IL-2 gamma (NSG) mice model, IL23mAb-T2A-PSMA-CAR T cells functioned significantly better than CAR T cells from the other groups and eradicated the tumor from these mice starting at day 14 post T cells injection and regained the body weight immediately. In IL23mAb-T2A-PSMA-CAR mice, CD45RO+ CD8+ T cells and CD127+ CD4+ CAR T cells were significantly increased. RNA sequencing revealed a difference expression pattern of genes in IL23mAb-T2A-PSMA-CAR mice. A reverse infusion experiment under the same model further proved the tumor eradication function of IL23mAb-T2A-PSMA-CAR T cells. CONCLUSIONS: We found that IL-23mAb combined PSMA CARs worked better than PSMA CAR only in Prostate Cancer Eradication, and we further discussed the mechanisms among different IL-23mAb combined PSMA CARs in Prostate Cancer Eradication.

The Effects of Neurokinin-1 Receptor Antagonist in an Experimental Autoimmune Cystitis Model Resembling Bladder Pain Syndrome/Interstitial Cystitis.

To identify the effects of the neurokinin-1 receptor (NK1R) antagonist aprepitant in treating pelvic pain, micturition symptoms, and bladder inflammation in mice with experimental autoimmune cystitis (EAC) similar to bladder pain syndrome/interstitial cystitis (BPS/IC). Female C57BL/6 mice were divided into the following three groups: normal control, EAC, and EAC plus aprepitant. EAC was induced in mice by duplicate immunization with bladder homogenate. In the EAC model group, EAC mice were given PBS by gavage once a day during the fourth week. In the EAC plus aprepitant group, aprepitant was administered instead of PBS in the same way. After 4 weeks, pelvic pain threshold and urination habits of mice were analyzed, as well as the bladder weight to body weight ratio, and histologic assessment of the expression of IL-1ß, TNF-α, intercellular adhesion molecule 1 (ICAM-1), and NK1R in bladder tissue. EAC mice mimicked the phenotype and pathophysiologic lesions of BPS/IC well. Compared to PBS-treated EAC mice, the mice treated with aprepitant exhibited higher pain threshold values, less number of total urine spots or small urine spots, lower bladder weight to body weight ratio, and reduced bladder inflammation with less mast cell infiltration and decreased expressions of IL-1ß, TNF-α, and ICAM-1 in bladder tissue. There was no difference in NK1R expression in bladders treated with or without aprepitant. The NK1R antagonist aprepitant relieved pelvic pain, urinary symptoms, and bladder inflammation in EAC mice. This indicated that NK1R may be a novel therapeutic target in BPS/IC treatment.

Unilateral pedal lymphangiography plus computed tomography angiography for location of persistent idiopathic chyle leakage not detectable by ordinary contrast computed tomography.

BACKGROUND: To identify the value of unilateral pedal lymphangiography (LPG) plus computed tomography angiography (CTA) in accurate depiction of persistent idiopathic chyluria undetectable by ordinary contrast CT. METHODS: Eighteen patients 44-63 years of age with persistent idiopathic chyluria who failed conservative management were included. Ordinary CT had not revealed a chyle leak. Cystoscopy, unilateral LPG, and post-LPG CT angiography (CTA) were sequentially performed. Ligation and stripping of the perirenal lymphatics were subsequently performed guided by lymphangiography and CTA. RESULTS: LPG and post-LPG CTA detected 17 unilateral and one bilateral chyle leaks in the 18 patients, with clear images of the communication of lymphatic vessels and the renal collecting or vascular system. The success rate was significantly better than cystoscopy (100% vs 50.0%, P = 0.005) or LPG alone (100% vs. 72.2%, P = 0.016). Chyluria resolved after surgery in all patients; no relapses were found. CONCLUSIONS: LPG plus post-LPG CTA accurately characterized perirenal lymphangiectasia that was not demonstrated by routine contrast-enhanced CT or not suitable for magnetic resonance imaging. Despite of its invasiveness, this method is a good diagnostic alternative to LPG in patients with persistent chyluria requiring surgery.

Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice.

The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund's adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund's adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic-pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1ß, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1ß, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in double-immunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC.

Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis.

The development and progression of bladder pain syndrome/interstitial cystitis (BPS/IC) is closely related to bladder inflammation. Intercellular adhesion molecule 1 (ICAM-1) is associated with bladder inflammation in BPS/IC. We investigated the effect of specific inhibition of ICAM-1 using an anti-ICAM-1 antibody (AIA) on bladder inflammation in a rat model of severe non-bacterial cystitis (NBC) resembling BPS/IC by evaluating the bladder inflammation grade, mast cell infiltration and related cytokines and receptors. We also compared the effects of AIA with the COX-2 inhibitor celecoxib and the neurokinin-1 receptor (NK1R) inhibitor aprepitant. Our NBC model was established by intraperitoneal injection of cyclophosphamide combined with intravesical protamine/lipopolysaccharide, which resulted in severe bladder inflammation and increased mast cell infiltration, similar to the pathological changes of BPS/IC. Inhibition of ICAM-1 by AIA significantly decreased the bladder inflammation grade and mast cell counts, which was accompanied by a reduction of purinergic receptors (P2X2/P2X3), prostaglandin E2, EP1/EP2 receptors, TNF-α, NK1R, and ICAM-1. Moreover, AIA showed superior effects to those of celecoxib and aprepitant treatment in improving the bladder inflammatory response. Our results suggest that ICAM-1 may play a critical role in bladder inflammation in severe NBC and may be used as a novel therapeutic target in non-bacterial bladder inflammation such as BPS/IC.